Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/24883
Title: Inhibition of Mitochondrial Complex III Blocks Neuronal Differentiation and Maintains Embryonic Stem Cell Pluripotency
Authors: Sandro, L. Pereira 
Grãos, Mário 
Rodrigues, Ana Sofia 
Anjo, Sandra I. 
Carvalho, Rui A. 
Oliveira, Paulo J. 
Arenas, Ernest 
Ramalho-Santos, João 
Issue Date: 2-Dec-2013
Publisher: Stefan Schlatt, University Hospital of Münster, Germany
Serial title, monograph or event: PLoS ONE
Volume: 8
Issue: 12
Abstract: The mitochondrion is emerging as a key organelle in stem cell biology, acting as a regulator of stem cell pluripotency and differentiation. In this study we sought to understand the effect of mitochondrial complex III inhibition during neuronal differentiation of mouse embryonic stem cells. When exposed to antimycin A, a specific complex III inhibitor, embryonic stem cells failed to differentiate into dopaminergic neurons, maintaining high Oct4 levels even when subjected to a specific differentiation protocol. Mitochondrial inhibition affected distinct populations of cells present in culture, inducing cell loss in differentiated cells, but not inducing apoptosis in mouse embryonic stem cells. A reduction in overall proliferation rate was observed, corresponding to a slight arrest in S phase. Moreover, antimycin A treatment induced a consistent increase in HIF-1α protein levels. The present work demonstrates that mitochondrial metabolism is critical for neuronal differentiation and emphasizes that modulation of mitochondrial functions through pharmacological approaches can be useful in the context of controlling stem cell maintenance/ differentiation.
URI: http://hdl.handle.net/10316/24883
ISSN: 1932-6203
Rights: openAccess
Appears in Collections:FCTUC Ciências da Vida - Artigos em Revistas Internacionais

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